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Advances in Diagnosing MS

MRI is currently the most effective tool for making a diagnosis of multiple sclerosis.

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With multiple sclerosis, it’s critical to be diagnosed as early as possible, so that treatment can begin and, ideally, stave off the progression of neurological damage and disability.

But this urgency presents a challenge for physicians, because there is currently no single test that results in a definitive diagnosis of MS. Add to that the fact that MS can manifest differently in different people, and you'll see that an accurate diagnosis is rarely straightforward and largely a process of elimination.

In 2000, a set of criteria, known as the McDonald Criteria for the Diagnosis of Multiple Sclerosis, aimed to spell out what’s needed to accurately diagnose MS in certain people with a specific manifestation of MS, called clinically isolated syndrome (CIS). Since then, the criteria have been refined to incorporate new research findings, expedite diagnosis, and avoid misdiagnosis.

More on Diagnosing MS

Types of MS

MS is an autoimmune disease in which the immune system attacks the myelin sheaths that protect nerve fibers in the brain, spinal cord, and optic nerve. The nerve fibers themselves can also be damaged or destroyed. This, in turn, slows or disrupts the transmission of nerve impulses from the brain, causing symptoms including fatigue, tingling and numbness, weakness, vision problems, and difficulty walking. Types of MS include:

Relapsing-remitting multiple sclerosis (RRMS) In relapsing-remitting multiple sclerosis, the most common type, symptoms tend to flare periodically, followed by stretches of complete or partial recovery. The vast majority — about 85 percent — of people with MS are initially diagnosed with RRMS.

Primary-progressive multiple sclerosis (PPMS) Those with PPMS experience steadily worsening symptoms with few or no recovery periods. Nerve damage is generally more focused in the spinal cord than in the brain and can cause more significant disability than RRMS. Approximately 10 percent to 15 percent of people with MS are diagnosed with PPMS.

Secondary-progressive multiple sclerosis (SPMS) Most people with RRMS eventually progress to secondary-progressive MS (SPMS), which involves a consistent worsening of symptoms. Flare-ups (periods of intensifying symptoms, also known as relapses or exacerbations) may occur, but are less frequent than in RRMS.

Clinically isolated syndrome (CIS) CIS refers to a first episode of neurologic symptoms that lasts at least 24 hours and is caused by inflammation or demyelination in the central nervous system (CNS). CIS can be monofocal, in which the person experiences a single neurologic sign or symptom — for example, an attack of optic neuritis — that’s caused by a single lesion. Or it can be multifocal, where the person experiences more than one sign or symptom — for example, an attack of optic neuritis accompanied by numbness or tingling in the legs — caused by lesions in more than one place.

In addition, there is growing research on a phenomenon known as radiologically isolated syndrome (RIS). In this case, findings on an MRI done for other reasons reveal lesions indicative of MS, but the person has no symptoms. As with CIS, someone with RIS may not go on to develop MS.

“RIS, CIS, established relapsing-remitting MS, and secondary-progressive MS are better thought of as stages of MS through which patients evolve,” says Jeffrey Cohen, MD, the director of experimental therapeutics at the Mellen Center for Multiple Sclerosis at the Cleveland Clinic in Ohio and cochair of the international panel that developed the 2017 McDonald Criteria.

“RIS is an MRI highly suggestive of MS but the person has no symptoms. CIS is the first attack. So, although one might suspect MS at the time of RIS and CIS, at that point, the diagnosis is not yet certain,” Dr. Cohen says.

Blood tests While there is no definitive blood test for MS, certain tests can help rule out other conditions that cause symptoms similar to those of MS, including Lyme disease, a group of diseases known as collagen-vascular diseases, certain rare hereditary disorders, and AIDS.

Magnetic resonance imaging (MRI) MRI scans use magnetic fields and radio waves to detect lesions in the brain that are indicative of MS. MRI is currently the most effective tool for making a diagnosis of the disease.

Cerebrospinal fluid test (CSF) For this test, a few tablespoons of spinal fluid are drawn from between the lower vertebrae with a syringe. The spinal fluid of people with MS usually contains elevated levels of certain antibodies, as well as a group of proteins called oligoclonal bands. There may also be certain proteins that are the breakdown products of myelin. Not all people with MS have these CSF abnormalities.

Implications of the New Criteria

Given the importance of early diagnosis and treatment, “catching” CIS is important, and this is where the McDonald Criteria come in. The main changes involve interpretation of MRIs and CSF tests.

The standard criteria for making an MS diagnosis include all the following:

Evidence of damage in at least two separate areas of the central nervous system (CNS), which includes the brain, spinal cord and optic nerves; evidence that the damage occurred at different points in time

Ruling out all other possible diagnoses

The key changes in the new McDonald Criteria include:

Substitution of positive findings of oligoclonal bands in the spinal fluid for finding lesions in two or more areas in some cases

Allowing both asymptomatic and symptomatic MRI lesions to be considered when determining the number of lesions and when they occurred

Including lesions in the brain’s outer layer, or cortex (called cortical lesions), as well as those next to the cortex (juxtacortical) when determining MRI criteria for how many lesions are visible

Cohen points out that even with the new criteria, MS remains a clinical diagnosis — not a laboratory or imaging-based diagnosis — and researchers continue to pursue ways to improve upon that.

“Current research is focusing on developing a blood test which would ideally turn up an abnormality found in people with MS,” he says. “We still very much need something like that so that we can make a definitive diagnosis.”

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